Institution
St. Jude Children's Research Hospital
Healthcare•Memphis, Tennessee, United States•
About: St. Jude Children's Research Hospital is a healthcare organization based out in Memphis, Tennessee, United States. It is known for research contribution in the topics: Population & Virus. The organization has 9344 authors who have published 19233 publications receiving 1233399 citations. The organization is also known as: St. Jude Children's Hospital & St. Jude Hospital.
Topics: Population, Virus, Cancer, Influenza A virus, Leukemia
Papers published on a yearly basis
Papers
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TL;DR: Structures are now available for many protein complexes in E1-E2-E3 cascades, revealing a series of modular building blocks and providing mechanistic insights into their functions.
Abstract: Covalent attachment of ubiquitin-like proteins (Ubls) is a predominant mechanism for regulating protein function in eukaryotes. Several structurally related Ubls, such as ubiquitin, SUMO, NEDD8, and ISG15, modify a vast number of proteins, altering their functions in a variety of ways. Ubl modifications can affect the target's half-life, subcellular localization, enzymatic activity, or ability to interact with protein or DNA partners. Generally, these diverse Ubls are covalently attached via their C termini to their targets by parallel, but specific, cascades involving three classes of enzymes known as E1, E2, and E3. Structures are now available for many protein complexes in E1-E2-E3 cascades, revealing a series of modular building blocks and providing mechanistic insights into their functions.
263 citations
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TL;DR: It is found that primary cultures of BM-derived MSC can be established with animal serum-free media containing fresh frozen plasma and platelets and can be replaced safely by FFPP in cultures of MSC for clinical purposes.
262 citations
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TL;DR: The studies presented here demonstrate that this region is also necessary and sufficient for the activation of Stat5A and Stat5B, and can disrupt Stat5 DNA binding activity, consistent with a role of Y-343 as a site of recruitment to the receptor.
Abstract: The cytoplasmic domain of the erythropoietin receptor (EpoR) contains a membrane-distal region that is dispensable for mitogenesis but is required for the recruitment and tyrosine phosphorylation of a variety of signaling proteins. The membrane-proximal region of 96 amino acids is necessary and sufficient for mitogenesis as well as Jak2 activation, induction of c-fos, c-myc, cis, the T-cell receptor gamma locus (TCR-gamma), and c-pim-1. The studies presented here demonstrate that this region is also necessary and sufficient for the activation of Stat5A and Stat5B. The membrane-proximal domain contains a single tyrosine, Y-343, which when mutated eliminates the ability of the receptor to couple Epo binding to the activation of Stat5. Furthermore, peptide competitions demonstrate that this site, when phosphorylated, can disrupt Stat5 DNA binding activity, consistent with a role of Y-343 as a site of recruitment to the receptor. Cells expressing the truncated, Y343F mutant (a mutant with a Y-to-F alteration at position 343) proliferate in response to Epo in a manner comparable to that of the controls. However, in these cells, Epo stimulation does not induce the appearance of transcripts for cis, TCR-gamma, or c-fos, suggesting a role for Stat5 in their regulation.
262 citations
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TL;DR: Although survivors had an increased time to pregnancy compared with their siblings, 292 of 455 participants with self-reported clinical infertility achieved a pregnancy, and increasing doses of uterine radiation and alkylating agent chemotherapy were strongly associated with infertility.
Abstract: Summary Background Previous studies have shown decreased pregnancy rates and early menopause in female cancer survivors; however, infertility rates and reproductive interventions have not been studied. We investigated infertility and time to pregnancy in female childhood cancer survivors, and analysed treatment characteristics associated with infertility and subsequent pregnancy. Methods The Childhood Cancer Survivor Study (CCSS) is a cohort study including 5 year cancer survivors from 26 Canadian and US institutions who were younger than 21 years at the time of diagnosis between Jan 1, 1970, and Dec 31, 1986, and a sibling control group. We included women aged 18–39 years who had ever been sexually active. We gathered demographic, medical, and reproductive data via a baseline questionnaire, and quantified exposure to alkylating agents and radiation therapy. Self-reported infertility, medical treatment for infertility, time to first pregnancy in survivors and siblings, and the risk of infertility in survivors by demographic, disease, and treatment variables were analysed. Findings 3531 survivors and 1366 female sibling controls who enrolled between Nov 3, 1992, and April 4, 2004, were included. Compared with their siblings, survivors had an increased risk (relative risk [RR] 1·48 [95% CI 1·23–1·78]; p 1 year of attempts at conception without success), which was most pronounced at early reproductive ages (RR 2·92 [95% CI 1·18–7·20], p=0·020, in participants ≤24 years; 1·61 [1·05–2·48], p=0·029, in those aged 25–29 years; and 1·37 [1·11–1·69], p=0·0035, in those aged 30–40 years). Despite being equally likely to seek treatment for infertility, survivors were less likely than were their siblings to be prescribed drugs for treatment of infertility (0·57 [95% CI 0·46–0·70], p Interpretation A more comprehensive understanding of infertility after cancer is crucial for counselling and decision making about future conception attempts and fertility preservation. Funding National Cancer Institute, American Lebanese Syrian Associated Charities, Swim Across America.
262 citations
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TL;DR: It is established that erythrocyte TPMT activity was significantly related to the amount of T PMT protein on Western blots of ERYthrocytes from patients with TPM T activities of 0.4-23 units/ml pRBC, and enhanced degradation of TPMt proteins encoded by TPMC*2 and TPMG*3A are established as mechanisms for lower TPM t protein and catalytic activity inherited by the predominant mutant alleles at the
Abstract: TPMT is a cytosolic enzyme that catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl compounds, including medications such as mercaptopurine and thioguanine. TPMT activity exhibits autosomal codominant genetic polymorphism, and patients inheriting TPMT deficiency are at high risk of potentially fatal hematopoietic toxicity. The most prevalent mutant alleles associated with TPMT deficiency in humans have been cloned and characterized (TPMT*2 and TPMT*3A), but the mechanisms for loss of catalytic activity have not been elucidated. In the present study, we established that erythrocyte TPMT activity was significantly related to the amount of TPMT protein on Western blots of erythrocytes from patients with TPMT activities of 0.4-23 units/ml pRBC (rs = 0.99; P < 0.001). Similarly, heterologous expression of wild-type (TPMT*1) and mutant (TPMT*2 and TPMT*3A) human cDNAs in yeast and COS-1 cells demonstrated comparable levels of TPMT mRNA but significantly lower TPMT protein with the mutant cDNAs. Rates of protein synthesis were comparable for wild-type and mutant proteins expressed in yeast and with in vitro translation in rabbit reticulocyte lysates. In contrast, pulse-chase experiments revealed significantly shorter degradation half-lives for TPMT*2 and TPMT*3A ( approximately 0.25 hr) compared with wild-type TPMT*1 (18 hr). The degradation of mutant proteins was impaired by ATP depletion and in yeast with mutant proteasomes (pre-1 strain) but unaffected by the lysosomal inhibitor chloroquine. These studies establish enhanced degradation of TPMT proteins encoded by TPMT*2 and TPMT*3A as mechanisms for lower TPMT protein and catalytic activity inherited by the predominant mutant alleles at the human TPMT locus.
262 citations
Authors
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Name | H-index | Papers | Citations |
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Richard A. Flavell | 231 | 1328 | 205119 |
David Baltimore | 203 | 876 | 162955 |
John C. Reed | 190 | 891 | 164382 |
Joan Massagué | 189 | 408 | 149951 |
Stuart H. Orkin | 186 | 715 | 112182 |
Douglas R. Green | 182 | 661 | 145944 |
Richard K. Wilson | 173 | 463 | 260000 |
Todd R. Golub | 164 | 422 | 201457 |
Robert G. Webster | 158 | 843 | 90776 |
Elaine R. Mardis | 156 | 485 | 226700 |
David Cella | 156 | 1258 | 106402 |
Rafi Ahmed | 146 | 633 | 93190 |
Ching-Hon Pui | 145 | 805 | 72146 |
Yoshihiro Kawaoka | 139 | 883 | 75087 |
Seth M. Steinberg | 137 | 936 | 80148 |